Four-component protein nanocages designed by programmed symmetry breaking

Area of Science:

• Protein engineering
• Nanotechnology
• Structural biology

Background:

• Protein trimers can form closed cages with specific symmetries (tetrahedral, octahedral, icosahedral).
• Viruses utilize higher triangulation numbers for complex architectures by breaking symmetry, a strategy not explored for other symmetries.

Purpose of the Study:

• To develop a general strategy for constructing higher triangulation number protein architectures based on regular polyhedra.
• To enable the creation of novel nanocage structures beyond naturally occurring symmetries.

Main Methods:

• Designing protein trimers capable of pseudosymmetrization.
• Assembling these trimers into closed cage-like structures with defined symmetries.
• Characterizing the resulting nanocages using electron microscopy.

Main Results:

• Successfully created T=4 protein cages with 48 (tetrahedral), 96 (octahedral), and 240 (icosahedral) subunits.
• Confirmed structures with specific diameters (33 nm, 43 nm, 75 nm) and complex subunit compositions (4 distinct chains, 6 interfaces).

Conclusions:

• A general design strategy for higher triangulation number nanocages has been established.
• This approach allows for the creation of sophisticated protein architectures with controllable symmetries.
• The developed nanocages hold potential for applications in vaccine development and targeted drug delivery.